Atherosclerotic blood vessels treated with percutaneous transluminal coronary angioplasty (PTCA) balloons (with or without stents) have been shown to have a better clinical outcome if they can be immediately treated with anti-restenosis drugs. This has led to designs of stent coatings incorporating slow release of paclitaxel and other anti-restenosis agents. Stent implementation or administration, however, carries a long term risk of spontaneous thrombosis, thereby requiring daily use of anti-platelet drugs.
Methods to deliver anti-restenosis agents (e.g. paclitaxel and rapamycin) without stents typically take the form of modified PTCA angioplasty balloon catheters such as double balloon catheters and porous balloons. These devices tend to be cumbersome and can cause additional vascular injury. More recently, drug-eluting balloons have been developed using conventional balloon catheters, usually via surface modification.
Preliminary findings have also demonstrated positive proof-of-concept data. Using a simple solvent coating procedure, Scheller et al. (Circulation. 2004 Aug. 17; 110(7):810-4. Epub 2004 Aug. 9) coated PTCA angioplasty balloon catheters with paclitaxel and proceeded to test them against bare metal stents in porcine coronary arteries. The coating was found to be safe and as effective in restenosis inhibition as drug eluting stents. However, efficacy of the drug eluting stents and the paclitaxel-coated balloon catheters were not directly compared. A clinical trial involving 52 patients was subsequently done comparing paclitaxel-coated balloon to uncoated balloons (Scheller et al., N Engl J Med. 2006 Nov. 16; 355(20):2113-24. Epub 2006 Nov. 13). After 12 months, major adverse cardiac events was 31% in the untreated controls and 4% in the paclitaxel-coated balloon group. A two-year follow-up with a total of 108 patients demonstrated continued restenosis inhibition (Scheller et al., Clin Res Cardiol. 2008 October; 97(10):773-81. Epub 2008 Jun. 5).
Currently, the drug-eluting balloons focus predominantly on 2 designs: drugs incorporated onto a porous surface and drugs incorporated into a “transfer” agent, such as iopromide (as a contrast agent). The DIOR® drug-eluting balloon is an example of the pore-incorporated paclitaxel, while the PACCOCATH® technology developed by Braun is an example of the latter design. Other transfer agents such as urea and shellac are also popular.
Nevertheless, there are some inherent limitations in the current designs. The paclitaxel-coated balloons inherently involve erratic (non-predictable) drug delivery. This is particularly troublesome because the bolus amount varies with the skill of the practitioner and thus the delivered dose is highly variable, which is undesirable. Further, there is no sustained drug delivery beyond the initial 2 to 3 days after administration of the balloons.
Therefore, there remains a need to provide for an improved bioactive-eluting device to overcome, or at least alleviates, the above problems.